DESCRIPTION: Functional analysis of a chromosomal region comprising 2% of the mouse genome will be conducted by saturation mutagenesis. Complementing types of mutations, chromosome deletions and point mutations, will be combined towards this end. First a series of 4 adjacent, radiation-induced deletion complexes will be generated on chromosome 5. This will be accomplished by implementation of an ES-cell-based technology the investigators have developed for the induction and selection of deletions encompassing loci of interest. A set of deletion stocks will be established that collectively span a 30 cM region on Chr.5. Second, an ENU mutagenesis screen will be performed, whereby mutagenized animals will be used in conjuction with the deletion sets to identify novel mutations on proximal Chr. 5. The identification of mutagenized chromosomes failing to complement nested deletion sets will then be used to localize particular ENU-induced mutations to intervals of approximately 0.3 cM. The goal will be to identify mutations affecting meiosis, embryonic development, seizure resistance and hearing. In a companion IRPG proposal, a screen for mutations affecting behavior will be performed.